Efficacy and safety of daratumumab, lenalidomide, and dexamethasone (D-Rd) in relapsed or refractory multiple myeloma (RRMM): Updated subgroup analysis of POLLUX based on cytogenetic risk.

person Jonathan L. Kaufman Winship Cancer Institute, Emory University, Atlanta, GA info_outline Jonathan L. Kaufman, Meletios A. Dimopoulos, Merav Leiba, James Morton, P. Joy Ho, Kihyun Kim, Philippe Moreau, Heather J Sutherland, Shinsuke Iida, Jin Seok Kim, H. Miles Prince, Nizar J. Bahlis, Ajai Chari, Herve Avet-Loiseau, Christopher Chiu, David Soong, Jon Ukropec, Ming Qi, Jesus San Miguel, Albert Oriol Rocafiguera

Authors person Jonathan L. Kaufman Winship Cancer Institute, Emory University, Atlanta, GA info_outline Jonathan L. Kaufman, Meletios A. Dimopoulos, Merav Leiba, James Morton, P. Joy Ho, Kihyun Kim, Philippe Moreau, Heather J Sutherland, Shinsuke Iida, Jin Seok Kim, H. Miles Prince, Nizar J. Bahlis, Ajai Chari, Herve Avet-Loiseau, Christopher Chiu, David Soong, Jon Ukropec, Ming Qi, Jesus San Miguel, Albert Oriol Rocafiguera Organizations Winship Cancer Institute, Emory University, Atlanta, GA, The National and Kapodistrian University of Athens, Athens, Greece, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel, Icon Cancer Care, South Brisbane, QLD, Australia, Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Hematology, University Hospital Hôtel-Dieu, Nantes, France, Leukemia/Bone Marrow Transplant Program, University of British Columbia, Vancouver, BC, Canada, Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea, Cabrini Hospital, Epworth HealthCare and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia, University of Calgary, Arnie Charbonneau Cancer Institute, Calgary, AB, Canada, Icahn School of Medicine at Mount Sinai, New York, NY, Unite de Genomique du Myelome, IUC-Oncopole, Toulouse, France, Janssen Research & Development, LLC, Spring House, PA, Janssen Global Medical Affairs, Horsham, PA, Clínica Universidad de Navarra-CIMA, IDISNA, CIBERONC, Pamplona, Spain, Institut Català d’Oncologia i Institut Josep Carreras, Hospital Germans Trias I Pujol, Barcelona, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: High-risk cytogenetic abnormalities confer poor outcomes in MM patients (pts). In POLLUX, D-Rd demonstrated significant clinical benefit, including prolonged progression-free survival (PFS) vs lenalidomide and dexamethasone (Rd), and tolerability in RRMM pts. We present a subgroup analysis of POLLUX, based on cytogenetic risk. Methods: Pts had ≥1 prior line of therapy. Cytogenetic risk was based on a combined analysis of fluorescence in situ hybridization/karyotype testing and next-generation sequencing (NGS). High-risk pts had t(4;14), t(14;16), or del17p abnormalities; standard (std)-risk pts did not meet high-risk criteria. Minimal residual disease (MRD; 10 –5 ) was assessed via NGS using clonoSEQ ® assay V2.0. Results: In POLLUX (D-Rd, n = 286; Rd, n = 283), 17.1% of pts in the D-Rd group and 20.1% of pts in the Rd group had high-risk abnormalities. After 44.3 months (mo) of median follow up, D-Rd prolonged PFS vs Rd in pts with high- (median 26.8 vs 8.8 mo; HR, 0.54 [95% CI, 0.32-0.91]; P = 0.0175) or std-risk (median not reached [NR] vs 19.9 mo; HR, 0.41 [95% CI, 0.31-0.55]; P <0.0001). Responses with D-Rd were deep, including higher rates of MRD negativity and sustained MRD negativity vs Rd (Table). D-Rd prolonged PFS in first relapse pts (high risk: median 46.0 vs 7.3 mo; HR, 0.26 [95% CI, 0.11-0.59]; P = 0.0005; std risk: median NR vs 20.6 mo; HR, 0.43 [95% CI, 0.28-0.66]; P <0.0001) and prolonged PFS2 vs Rd in high- (median 38.3 vs 22.1 mo; HR, 0.53 [95% CI, 0.30-0.93]; P = 0.0249) or std-risk (median NR vs 33.8 mo; HR, 0.53 [95% CI, 0.39-0.72]; P <0.0001) pts. Additional data will be presented. Conclusions: D-Rd demonstrates significant efficacy in high-risk RRMM. Among high-risk pts, MRD negativity was only achieved with D-Rd. Clinical trial information: NCT02076009 Std risk High risk D-Rd (n = 204) Rd (n = 178) P value D-Rd (n = 48) Rd (n = 55) P value ORR, % 93.6 79.2 <0.0001 87.5 69.1 0.0115 ≥CR, % 59.3 27.0 43.8 9.1 ≥sCR, % 31.4 13.5 29.2 1.8 ≥≥VGPR, % 82.8 55.1 <0.0001 70.8 32.7 0.0003 MRD neg, % a 32.9 8.2 <0.0001 28.6 0 <0.0001 ≥MRD neg (≥6 mo), % a 17.9 1.1 <0.0001 12.2 0 0.0082 ≥MRD neg (≥12 mo), % a 14.0 0.5 <0.0001 10.2 0 0.0188 a Intent-to-treat population.